S238: MATCHED RELATED VERSUS UNRELATED VERSUS HAPLOIDENTICAL DONORS FOR ALLOGENEIC TRANSPLANTATION IN AML PATIENTS ACHIEVING FIRST COMPLETE REMISSION AFTER TWO INDUCTION COURSES: A STUDY FROM THE ALWP/EBMT
Authors: A. Nagler, M. Labopin, S. Mielke, J. Passweg, D. Blaise, T. Gedde-Dahl, J. J. Cornelissen, U. Salmenniemi, I. Yakoub-Agha, P. Reményi, G. Socié, G. Van Gorkom, H. Labussière-Wallet, X.-J. Huang, M. Thérèse Rubio, J. L Byrne, C. Craddock, L. Griskevicius, F. Ciceri, M. Mohty
Journal: HemaSphere (2022)

Background: Transplantation (HSCT) outcome is significantly inferior in AML patients (pts) who required 2 rather than 1 induction course to achieve CR1, with a higher relapse (RI) and lower leukemia-free (LFS) and overall survival (OS) and lower graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS). Aims: To allocate the best donor for HSCT in AML pts achieving CR1 after 2 inductions comparing matched related sibling donors (MSD) with 9-10/10 HLA compatible unrelated donors (UD) and non-T cell depleted haploidentical (Haplo) donors, respectively. Methods: This was a retrospective analysis including adult pts aged ≥18 years with AML undergoing HSCT while in CR1 achieved after 2 inductions during the period 2010-2020. Allografts were from MSD, UD or Haplo donors. Multivariate analysis (MVA) adjusting for potential confounding factors was performed using a Cox’s proportional-hazards regression model for main outcomes. Results: 1295 pts were included: MSD (n=428), UD 10/10 (n=554), UD 9/10 (n=135), Haplo (n=178). Median follow up was 48.4, 46.0,40.5 and 35.2 months, respectively. Median age was 52.1, 53.8, 52.2 and 49.5 years, respectively. The 4 groups did not differ with respect to pts’ gender, type of AML, cytogenetics, and performance status. Haplo transplants were performed more recently, with more BM grafts and lower frequency of pt CMV seropositivity. Post-transplant cyclophosphamide (PTCy) was the main anti GVHD prophylaxis in HSCT from Haplo donors, while in vivo T-cell depletion was more frequently used in transplants from UD. Myeloablative conditioning was less frequently used in transplants from UD and time from diagnosis to HSCT was shorter in transplants from MSD. Cumulative incidence of ANC >0.5x109/L at day 30 was 98.1%, 98.5%, 95.5% and 92.1%, respectively (global P value=0.03). Univariate analysis of 2- and 5-year outcomes after transplantation are given in Table 1. On MVA, acute (a) GVHD II-IV but not III-IV was higher in all groups compared to MSD: UD 9/10, HR=2.53; 95% CI 1.68-3.82, P<0.0001; UD 10/10, HR=1.96; 95% CI 1.42-2.69, P<0.0001 and Haplo HR=2.15; 95% CI 1.41-3.3, P=0.0004. Incidence of extensive chronic (c) GVHD was significantly higher in UD 9/10 (HR=2.52; 95% CI 1.55-4.11, P=0.0002) and UD 10/10 (HR=1.48; 95% CI 1.03-2.13, P=0.036) and cGVHD all grades was higher in UD 9/10 vs MSD (HR=1.77; 95% CI 1.26-2.49, P=0.0009), while it did not differ in Haplo transplants. Non-relapse mortality (NRM) was higher in HSCT from UD 10/10, 9/10 and Haplo donors compared with those from MSD (HR= 1.75; 95% CI 1.16-2.63, P= 0.007, HR =2.22; 95% CI 1.29-3.83, P= 0.004 and HR=2.53; 95% CI 1.47-4.34, P=0.0008), respectively. RI, LFS and OS did not differ significantly between donor types: RI HR=0.84, P=0.18; HR=0.9, P=0.59 and HR=0.76, P=0.17 in UD 10/10, UD 9/10 and Haplo vs MSD, respectively. LFS HR=1.02, P=0.87; HR=1.15, P=0.35 and HR=1.11, P=0.49 and OS HR=1.12, P=0.3, HR=1.27, P=0.14 and HR=1.33, P=0.081, respectively. Finally, GRFS was lower in HSCT from UD 9/10 (HR=1.56, 95% CI 1.20-2.03, P<0.001) but not in those from UD 10/10 (HR=1.13, P=0.22) and Haplo donors (HR=1.12, P=0.43) compared to MSD, respectively. Main cause of death in all groups was original disease, followed by infections, and GVHD. Image:Summary/Conclusion: In AML patients undergoing allogeneic transplantation in CR1 achieved after two induction courses which has been shown to be a poor prognostic factor, and those who do not have an MSD, HLA matched UD and Haplo donors are comparable alternatives. 40-50% of these pts achieved long term LFS.